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Expanding horizons in complement drug discovery: challenges and emerging strategies

Lookup NU author(s): Professor Claire Harris

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

© 2017 Springer-Verlag GmbH Germany The complement system is best known for its role in innate immunity, providing a first line of defence against infection, maintaining tissue homeostasis by flagging apoptotic cells and debris for removal, and orchestrating crosstalk between adaptive and innate immunity. In a growing number of diseases, complement is known to drive pathogenesis or to contribute as an inflammatory amplifier of a disease trigger. Association of complement with common and devastating diseases has driven an upsurge in complement drug discovery, but despite a wealth of knowledge in the complexities of the cascade, and many decades of effort, very few drugs have progressed to late-stage clinical studies. The reasons for this are becoming clear with difficulties including high target concentration and turnover, lack of clarity around disease mechanism and unwanted side effects. Lessons learnt from drugs which are either approved, or are currently in late-stage development, or have failed and dropped off the drug development landscape, have been invaluable to drive a new generation of innovative drugs which are progressing through clinical development. In this review, the challenges associated with complement drug discovery are discussed and the current drug development landscape is reviewed. The latest approaches to improve drug characteristics are explored and those agents which employ these technologies to improve accessibility to patients are highlighted.


Publication metadata

Author(s): Harris CL

Publication type: Article

Publication status: Published

Journal: Seminars in Immunopathology

Year: 2018

Volume: 40

Issue: 1

Pages: 125-140

Print publication date: 01/01/2018

Online publication date: 06/10/2017

Acceptance date: 19/09/2017

Date deposited: 21/12/2017

ISSN (print): 1863-2297

ISSN (electronic): 1863-2300

Publisher: Springer Verlag

URL: https://doi.org/10.1007/s00281-017-0655-8

DOI: 10.1007/s00281-017-0655-8


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